ABC | Volume 112, Nº6, June 2019

760 Original Article Rajão et al Subclinical thyroid dysfunction and arrhythmias Arq Bras Cardiol. 2019; 112(6):758-766 hours after a 75 g load of anhydrous glucose ≥ 200 mg/dL, or hemoglobin A1c ≥ 6.5%) or the use of insulin or oral/subcutaneous hypoglycemic drugs. Arterial hypertension was defined by a self-reported medical diagnosis of hypertension, use of anti-hypertensive agents, or blood pressure ≥ 140/90 mmHg. Dyslipidemia was defined as total serum cholesterol ≥ 200 mg/dL or triglycerides ≥ 150 mg/dL or LDL cholesterol ≥ 130 mg/dL, or the use of hypolipidemic medication. Congestive heart failure, coronary artery disease, and chronic obstructive pulmonary disease were defined by a self-reported medical diagnosis. Chagas disease was defined by positive serology in the Chagas test – ELISA assay. Excessive alcohol use was defined as the intake of more than 140 g of alcohol per week for women and more than 210 g of alcohol per week for men. Medications considered for statistical adjustments were those that could interfere with thyroid or cardiac function and included antiarrhythmic drugs, β -blockers other than propranolol (which had been excluded previously), β 2-agonists, adrenergic agonists and nondihydropyridine calcium channel blockers, lithium carbonate, potassium iodide, amiodarone, interferon- α , systemic glucocorticoids, dopaminergic agonists, carbamazepine, and oxcarbazepine. 27,28 Statistical analysis The statistical analysis was performed using the STATA™ software, v. 12.0. The data are described as medians and interquartile ranges or proportions, since they did not present a normal distribution, according to test of Shapiro‑Wilk. The nonparametric tests of Mann-Whitney and Kruskal‑Wallis were used to compare medians, Pearson’s chi-squared and Fisher’s exact tests to compare proportions, and Spearman's correlation coefficient to estimate correlations between continuous variables. Logistic regression analysis was delineated between SCHyperTh or SCHypoTh and serum TSH and FT4 levels and the presence of arrhythmias/ electrocardiographic abnormalities. Age, sex, skin color, body mass index (BMI), smoking status, excessive alcohol use, comorbidities (dyslipidemia, diabetes, hypertension, coronary disease, congestive heart failure, chronic obstructive pulmonary disease, and Chagas disease), and medication use were considered for adjustment. The p value < 0.20 was considered for the multivariate model, and statistical significance was p < 0.05. Subgroup analyses were performed for older individuals (age 65–74 years) and those with extreme TSH values (< 0.1 μU/mL or > 10 μU/mL). Results This study included 13,341 (88.32%) of the 15,105 participants enrolled at the baseline of the ELSA-Brasil study. The 1,764 excluded participants are shown in Figure 1. The profile of the participants for the overall study population categorized by thyroid function group is shown in Table 1. STD was found in 891 (6.68%) participants, with a greater prevalence of SCHypoTh (5.23%) over SCHyperTh (1.45%). SCHypoTh was slightly associated with older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02‑1.04), female sex (OR 1.18, 95% CI 1.01- 1.38), higher BMI (OR 1.03, 95% CI 1.01-1.04), and white skin color (OR 1.30, 95% CI 1.10‑1.55) when compared to the euthyroidism. Black skin color (OR 0.56, 95% CI 0.41- 0.75) and smoking (OR 0.72, 95% CI 0.56-0.94) were independently and negatively correlated with SCHypoTh. SCHyperTh was slightly associated with older age (OR 1.02, 95% CI 1.01-1.04), female sex (OR 1.71, 95% CI 1.26- 2.31), and black skin color (OR 1.61, 95% CI 1.11- 2.33). White skin color (OR 0.71, 95% CI 0.50-0.99) and non-smoking (OR 0.65, 95% CI 0.49-0.88) were independently and negatively associated with SCHyperTh. Increased BMI was associated with SCHyperTh only in the univariate analysis (OR 1.03, 95% CI 1.01-1.04) (Table 1). There were no significant differences in the HR medians of participants with normal thyroid function (35–130 bpm, median 70), SCHypoTh (42.5–111 bpm, median 70; p = 0.087) and SCHyperTh (42–104 bpm, median 71.5, p = 0.084). No correlation was found between HR and serum TSH or FT4 values, whether for the total study population or within each STD group. The multivariate linear regression indicated a relationship between TSH levels and HR in the participants with SCHypoTh (p = 0.001, after adjustment). No relationship was found between TSH levels and HR in the SCHyperTh group, or between FT4 levels and HR in any of the groups. Tachycardia was found in 3.10% of the participants and was not associated with STD, even among older adults or in those with extreme TSH values, as shown in Table 2. Likewise, bradycardia (14,72%) was not significantly associated with STD, even in those subgroups. The relationship between TSH and FT4 levels and heart rate is shown in Table 3. Median TSH levels were significantly higher for individuals with tachycardia compared to those with normal HR, even after adjustments, and medians for FT4 levels were significantly higher in individuals with tachycardia. Considering the 11,795 ECGs analyzed in this study, no abnormality was associated with STD (Table 4), even in the subgroup of older adults or those with extreme TSH values. The only correlation found was a lower frequency of branch blocks in older adults with SCHypoTh compared to those who were euthyroid (14.29% vs. 26.13%; adjusted OR 0.44, 95% CI 0.24-0.80; p = 0.007). A sensitivity analysis was performed excluding all participants in use of antiarrhythmic drugs, β -blockers, β 2-agonists, adrenergic agonists and nondihydropyridine, calcium channel blockers, lithium carbonate, potassium iodide, amiodarone, interferon- α , systemic glucocorticoids, dopaminergic agonists, carbamazepine, and oxcarbazepine, and most of the results were the same, without any association between STD and abnormalities in ECG, and no correlation or relationship was found between HR and serum TSH or FT4 values, whether for the total study population or within each STD group. The only association found was the lower frequency of bradycardia (HR < 60 bpm) in participants with SCHyperTh compared to those who were euthyroid (8,23% vs. 13,54%; adjusted OR 0.62, 95% CI 0.41-0.93; p = 0.021).